Recent advances in gene therapy


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Recent advances in gene therapy

  2. 2. Gene therapy is an experimental technique that uses genes to treat or prevent disease. In the future, this technique may allow doctors to treat a disorder by inserting a gene into a patients cells instead of using drugs or surgery. Gene therapy was first conceptualized in 1972 Researchers are testing several approaches to gene therapy, including: Replacing a mutated gene that causes disease with a healthy copy of the gene. Inactivating, or “knocking out,” a mutated gene that is functioning improperly. Introducing a new gene into the body to help fight a disease. What Is Gene Therapy
  3. 3. Although early clinical failures led many to dismiss gene therapy as over-hyped, clinical successes since 2006 have bolstered new optimism in the promise of gene therapy. These include successful treatment of patients with the retinal disease, X-linked SCID, adrenoleukodystrophy, chronic lymphocytic leukemia(CLL), acute lymphocytic leukemia(ALL), multiple myeloma and Parkinson's disease. These recent clinical successes have led to a renewed interest in gene therapy, with several articles in scientific and popular publications calling for continued investment in the field.
  4. 4. Types Of Gene Therapy Gene therapy may be classified into two types: 1. Somatic gene therapy - the therapeutic genes are transferred into the somatic cells, or body, of a patient. Any modifications and effects will be restricted to the individual patient only, and will not be inherited by the patient's offspring or later generations 2. Germ line gene therapy - sperm or eggs, are modified by the introduction of functional genes, which are integrated into their genomes. This would allow the therapy to be heritable and passed on to later generations
  5. 5. Gene Therapy Depends on Delivery of Corrective Genes Viral vectors are a tool commonly used by molecular biologists to deliver genetic material into cells. This process can be performed inside a living organism (in vivo) or in cell culture (in vitro). Viruses have evolved specialized molecular mechanisms to efficiently transport their genomes inside the cells they infect
  6. 6. Viruses are used as Delivery Tolls Viruses are used as vectors to introduce the genetic material inside the bodies. These viruses are inactivated, they are not able to reproduce 1. Adenoviruses 2. Herpes viruses - DNA tumor viruses 3. Retroviruses - RNA tumor viruses
  7. 7. First Approved Gene Therapy On September 14, 1990 at the U.S. National Institutes of Health, W. French Anderson M.D. and his colleagues R. Michael Blaese, M.D., C. Bouzaid, M.D., and Kenneth Culver, M.D., performed the first approved gene therapy procedure on four-year old Ashanthi DeSilva, Born with a rare genetic disease called severe combined immunodeficiency (SCID) What did they do In Ashanthi's gene therapy procedure, doctors removed white blood cells from the child's body, let the cells grow in the laboratory, inserted the missing gene into the cells, and then infused the genetically modified blood cells back into the patient's bloodstream.
  8. 8. A success story As of early 2007, she was still in good health, and she was attending college. Some would state that the study is of great importance despite its indefinite results, if only because it demonstrated that gene therapy could be practically attempted without adverse consequences
  9. 9. 'mending broken hearts' by using gene therapy Novel techniques to “mend broken hearts” using gene therapy and stem cells represent a major new frontier in the treatment of heart disease It was achieved by the researchers at Gladstone Institute of Cardiovascular Disease in California They were able to re-programme scar-forming cells into heart muscle cells, some of which were capable of transmitting the kind of electrical signals that make the heart beat They performed on a live mice, transforming scar-forming cells, called fibroblasts, into beating heart muscle cells They injected three genes (cocktail of genes) into the heart of live mice that had been damaged by heart attack, fibroblasts could be turned into working heart cells. Researchers said that the “cocktail of genes” used to regenerate cells could one day be replaced with “small drug-like molecules” that would offer safer and easier delivery
  10. 10. First Real-Time MRI-Guided Gene Therapy for Brain Cancer Neurosurgeons at the University of California, San Diego School of Medicine and UC San Diego Moores Cancer Center are among the first in the world to utilize real-time magnetic resonance imaging (MRI) guidance for delivery of gene therapy as a potential treatment for brain tumors Using MRI navigational technology, neurosurgeons can inject Toca 511 (vocimagene amiretrorepvec), a novel investigational gene therapy, directly into a brain malignancy The new approach offers a precise way to deliver a therapeutic virus designed to make the tumor susceptible to cancer-killing drugs
  11. 11. Toca 511 is a retrovirus engineered to selectively replicate in cancer cells, such as glioblastomas. Toca 511 produces an enzyme that converts an anti-fungal drug, flucytosine (5-FC), into the anti-cancer drug 5-fluorouracil (5-FU). After the injection of Toca 511, the patients are treated with an investigational extended- release oral formulation of 5-FC called Toca FC. Cancer cell killing takes place when 5-FC comes into contact with cells infected with Toca 511.
  12. 12. UCLA researchers combine cellular and gene therapies to develop treatment for breast cancer Carol Kruse, a professor of neurosurgery and member of the Jonsson Cancer Center and the UCLA Brain Research Institute led the research on breast cancer Breast cancer is the most common form of cancer in women, and metastasis is a major cause of health deterioration and death from the disease Cellular therapy and gene therapy were used together to treat breast cancer Cellular therapy is a type of immunotherapy that uses T cells, the foot soldiers of the immune system, that have been sensitized in the laboratory to kill breast cancer cells. These sensitized T cells are injected into the parts of the brain to which cancer has spread. The research shows that the T cells can move through tissue and recognize and directly kill the tumor cells
  13. 13. stem cell gene therapy gives hope to prevent inherited neurological disease Scientists from The University of Manchester have used stem cell gene therapy to treat a fatal genetic brain disease It was used to treat Sanfilippo – a fatal inherited condition which causes progressive dementia in children Sanfilippo, is currently untreatable mucopolysaccharide (MPS) disease It is caused by the lack of SGSH enzyme in the body which helps to breakdown and recycle long chain sugars, such as heparan sulphate (HS) Children with the condition build up and store excess HS throughout their body from birth which affects their brain and results in progressive dementia and hyperactivity, followed by losing the ability to walk and swallow
  14. 14. Researchers have developed a stem cell gene therapy which overproduces the SGSH enzyme specifically in bone marrow white blood cells to increase SGSH enzyme from bone marrow transplants, and to target it to the cells that traffic into the brain It was seen that mice treated by this method produce five times the normal SGSH enzyme levels in the bone marrow and and 11 per cent of normal levels in the brain The enzyme is taken up by affected brain cells and is enough to correct brain HS storage and neuro inflammation to near normal levels and completely corrects the hyperactive behaviour in mice with Sanfilippo
  15. 15. Mucopolysaccharidosis Type IIIA potential gene therapy Mucopolysaccharidosis Type IIIA (MPSIIIA) is a metabolic disorder in which the body is missing an enzyme that is required to break down long chains of sugars known as glycosaminoglycans The glycosaminoglycans collect in the body and cause damage, particularly in the brain if not broken Fàtima Bosch and colleagues at Universitat Autònoma de Barcelona in Spain developed a form of gene therapy to replace the enzyme that is missing in MPSIIIA They injected the replacement gene into the cerebrospinal fluid that surrounds the brain and spinal cord This study demonstrates that gene therapy can be delivered to the brain through the cerebrospinal fluid and suggests that this approach could potentially be used as a therapy for MPSIIIA
  16. 16. IS GENE THERAPY TOTALLY SAFE ?? Although gene therapy is a promising treatment option for a number of diseases (including inherited disorders, some types of cancer, and certain viral infections), the technique remains risky and is still under study to make sure that it will be safe and effective. Gene therapy is currently only being tested for the treatment of diseases that have no other cures
  17. 17. Technical Difficulties in Gene Therapy Gene delivery: Successful gene delivery is not easy or predictable, even in single-gene disorders. For example, although the genetic basis of cystic fibrosis is well known, the presence of mucus in the lungs makes it physically difficult to deliver genes to the target lung cells. Delivery of genes for cancer therapy may also be complicated by the disease being present at several sites. Gene-therapy trials for X-linked severe combined immunodeficiency (X-SCID), however, have been more successful
  18. 18. Problems with Gene Therapy Short Lived Hard to rapidly integrate therapeutic DNA into genome and rapidly dividing nature of cells prevent gene therapy from long time Would have to have multiple rounds of therapy Immune Response new things introduced leads to immune response increased response when a repeat offender enters the gene might be over-expressed (toxicity) Viral Vectors patient could have toxic, immune, inflammatory response also may cause disease once inside
  19. 19. Multigene Disorders Heart disease, high blood pressure, Alzheimer’s, arthritis and diabetes are hard to treat because you need to introduce more than one gene
  20. 20. Do not forget Genes can be Unpredictable ?